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At least 217 records · Page 12

Mesh Generation for Microstructures

A parallel, adaptive overlay grid procedure is proposed for use in generating all-hex meshes for stochastic (SVE) and representative (RVE) volume elements in computational materials modeling. The mesh generation process is outlined including several new advancements such as data filtering to improve mesh quality from voxelated and 3D image sources, improvements to the primal contouring method for constructing material interfaces and pillowing to improve mesh quality at boundaries. We show specific examples in crystal plasticity and syntactic foam modeling that have benefitted from the proposed mesh generation procedure and illustrate results of the procedure with several practical mesh examples.

36 MATERIALS SCIENCE↗

Attention-based 3D – convolutional neural network model for mechanical property predictions using visible light images in metal additive manufacturing

Additive manufacturing (AM), while commonly used for rapid prototyping and creating components with complex geometries, has not been widely adopted for critical applications across the aerospace, automotive, defense, energy, and medical industries. This is, in part, due to the challenges of controlling flaws and uncertainty in the mechanical behavior of additively manufactured components. In recent years, there has been an increase in research aimed at predicting the final mechanical properties of additively manufactured components during the printing process. To address these issues, a 3D-CNN model was trained using low-cost in situ visible-light camera data, anomaly classifications, and the chosen process parameters to predict the ultimate tensile strength (UTS), yield strength (YS), total elongation (TE), and uniform elongation (UE). The 3D-CNN layers of the model employed attention mechanisms to prioritize features in the data, thereby improving prediction accuracy. Furthermore, the effect of each process parameter and anomaly class is investigated using attention-based dynamic sigmoid weighted gates to interpret the influence each class has on the final prediction. Different combinations of the in situ data were fed into the 3D-CNN, with varying amounts of image layers, to determine the ideal combination for predicting mechanical properties in situ. Here, the 3D-CNN model achieved mean absolute percentage errors (MAPE) below 5% for both UTS and YS while using only a single camera input and under half of the available image layers.

36 MATERIALS SCIENCE↗

3D TEM reconstruction and segmentation process of laminar bio-nanocomposites

The microstructure of laminar bio-nanocomposites (Poly (lactic acid)(PLA)/clay) depends on the amount of clay platelet opening after integration with the polymer matrix and determines the final properties of the material. Transmission electron microscopy (TEM) technique is the only one that can provide a direct observation of the layer dispersion and the degree of exfoliation. However, the orientation of the clay platelets, which affects the final properties, is practically immeasurable from a single 2D TEM image. This issue can be overcome using transmission electron tomography (ET), a technique that allows the complete 3D characterization of the structure, including the measurement of the orientation of clay platelets, their morphology and their 3D distribution. ET involves a 3D reconstruction of the study volume and a subsequent segmentation of the study object. Currently, accurate segmentation is performed manually, which is inefficient and tedious. The aim of this work is to propose an objective/automated segmentation methodology process of a 3D TEM tomography reconstruction. In this method the segmentation threshold is optimized by minimizing the variation of the dimensions of the segmented objects and matching the segmented V{sub clay} (%) and the actual one. The method is first validated using a fictitious set of objects, and then applied on a nanocomposite.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Phase-contrast 3D tomography of HeLa cells grown in PLLA polymer electrospun scaffolds using synchrotron X-rays

Advanced imaging is useful for understanding the three-dimensional (3D) growth of cells. X-ray tomography serves as a powerful noninvasive, nondestructive technique that can fulfill these purposes by providing information about cell growth within 3D platforms. There are a limited number of studies taking advantage of synchrotron X-rays, which provides a large field of view and suitable resolution to image cells within specific biomaterials. In this study, X-ray synchrotron radiation microtomography at Diamond Light Source and advanced image processing were used to investigate cellular infiltration of HeLa cells within poly L-lactide (PLLA) scaffolds. This study demonstrates that synchrotron X-rays using phase contrast is a useful method to understand the 3D growth of cells in PLLA electrospun scaffolds. Two different fiber diameter (2 and 4 µm) scaffolds with different pore sizes, grown over 2, 5 and 8 days in vitro , were examined for infiltration and cell connectivity. After performing visualization by segmentation of the cells from the fibers, the results clearly show deeper cell growth and higher cellular interconnectivity in the 4 µm fiber diameter scaffold. Finally, this indicates the potential for using such 3D technology to study cell–scaffold interactions for future medical use.

3D culture↗

Measurement with microscopic MRI and simulation of flow in different aneurysm models

Purpose: The impact and the development of aneurysms depend to a significant degree on the exchange of liquid between the regular vessel and the pathological extension. A better understanding of this process will lead to improved prediction capabilities. The aim of the current study was to investigate fluid-exchange in aneurysm models of different complexities by combining microscopic magnetic resonance measurements with numerical simulations. In order to evaluate the accuracy and applicability of these methods, the fluid-exchange process between the unaltered vessel lumen and the aneurysm phantoms was analyzed quantitatively using high spatial resolution. Methods: Magnetic resonance flow imaging was used to visualize fluid-exchange in two different models produced with a 3D printer. One model of an aneurysm was based on histological findings. The flow distribution in the different models was measured on a microscopic scale using time of flight magnetic resonance imaging. The whole experiment was simulated using fast graphics processing unit-based numerical simulations. The obtained simulation results were compared qualitatively and quantitatively with the magnetic resonance imaging measurements, taking into account flow and spin–lattice relaxation. Results: The results of both presented methods compared well for the used aneurysm models and the chosen flow distributions. The results from the fluid-exchange analysis showed comparable characteristics concerning measurement and simulation. Similar symmetry behavior was observed. Based on these results, the amount of fluid-exchange was calculated. Depending on the geometry of the models, 7% to 45% of the liquid was exchanged per second. Conclusions: The result of the numerical simulations coincides well with the experimentally determined velocity field. The rate of fluid-exchange between vessel and aneurysm was well-predicted. Hence, the results obtained by simulation could be validated by the experiment. The observed deviations can be caused by the noise in the measurement and by the limited resolution of the simulation. The resulting differences are small enough to allow reliable predictions of the flow distribution in vessels with stents and for pulsed blood flow.

60 APPLIED LIFE SCIENCES↗

A tracking system to calculate patient skin dose in real-time during neurointerventional procedures using a biplane x-ray imaging system

Purpose: Neurovascular interventional procedures using biplane fluoroscopic imaging systems can lead to increased risk of radiation-induced skin injuries. The authors developed a biplane dose tracking system (Biplane-DTS) to calculate the cumulative skin dose distribution from the frontal and lateral x-ray tubes and display it in real-time as a color-coded map on a 3D graphic of the patient for immediate feedback to the physician. The agreement of the calculated values with the dose measured on phantoms was evaluated. Methods: The Biplane-DTS consists of multiple components including 3D graphic models of the imaging system and patient, an interactive graphical user interface, a data acquisition module to collect geometry and exposure parameters, the computer graphics processing unit, and functions for determining which parts of the patient graphic skin surface are within the beam and for calculating dose. The dose is calculated to individual points on the patient graphic using premeasured calibration files of entrance skin dose per mAs including backscatter; corrections are applied for field area, distance from the focal spot and patient table and pad attenuation when appropriate. The agreement of the calculated patient skin dose and its spatial distribution with measured values was evaluated in 2D and 3D for simulated procedure conditions using a PMMA block phantom and an SK-150 head phantom, respectively. Dose values calculated by the Biplane-DTS were compared to the measurements made on the phantom surface with radiochromic film and a calibrated ionization chamber, which was also used to calibrate the DTS. The agreement with measurements was specifically evaluated with variation in kVp, gantry angle, and field size. Results: The dose tracking system that was developed is able to acquire data from the two x-ray gantries on a biplane imaging system and calculate the skin dose for each exposure pulse to those vertices of a patient graphic that are determined to be in the beam. The calculations are done in real-time with a typical graphic update time of 30 ms and an average vertex separation of 3 mm. With appropriate corrections applied, the Biplane-DTS was able to determine the entrance dose within 6% and the spatial distribution of the dose within 4% compared to the measurements with the ionization chamber and film for the SK150 head phantom. The cumulative dose for overlapping fields from both gantries showed similar agreement. Conclusions: The Biplane-DTS can provide a good estimate of the peak skin dose and cumulative skin dose distribution during biplane neurointerventional procedures. Real-time display of this information should help the physician manage patient dose to reduce the risk of radiation-induced skin injuries.

60 APPLIED LIFE SCIENCES↗

In situ imaging of three dimensional freeze printing process using rapid x-ray synchrotron radiography

Three dimensional freeze printing (3DFP) combines the advantages of freeze casting and additive manufacturing to fabricate multifunctional aerogels. Freeze casting is a cost-effective, efficient, and versatile method capable of fabricating micro-scale porous structures inside the aerogels for many different applications. The 3DFP provided the capability of fabricating highly customized geometries with controlled microporous structures as well. However, there are still many unexplained phenomena and features because of the complexity of post-processes and indirect observation methods. This study demonstrates the design and construction of the in situ imaging systems, which use the x-ray synchrotron radiography to observe freeze casting and 3DFP processes. With the advantages provided by the in situ x-ray imaging techniques, the ice crystal growth with its unique lamellar structures can be observed during the freeze casting process. Here, the movement of freeze front, material deposition, and growth of ice crystals can also be visualized during the inkjet-based 3DFP process.

3D printing↗

X-ray Phase Contrast Imaging of Calcified Tissue and Biomaterial Structure in Bioreactor Engineered Tissues

Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. These techniques allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems and will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. Furthermore, these results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.

alginate microbeads↗

Physics-Informed and Data-Driven Prediction of Residual Stress in Three-Dimensional Machining

Efficient and reliable prediction of machining-induced residual stress (RS) is a key requirement for truly integrated computational materials engineering (ICME). Currently available process modeling approaches, including empirical, analytical, and numerical methodologies lack predictive power and require substantial calibration and validation data. Moreover, most model-based approaches consider only two-dimensional (2D) (i.e., orthogonal), cutting processes. Meanwhile, industrial processes such as milling, turning, and drilling are inherently three-dimensional (3D). The present work attempts to bridge the gap between 2D and 3D through careful consideration of the process physics, including geometric, kinematic, and size-effect constraints to realize robust prediction of how RS develops in 3D machining. Using a novel in-situ experimental technique and digital image correlation (DIC) to determine equivalent Hertzian contact widths, contact pressures, and friction coefficients, the proposed methodology leverages a discretized conversion algorithm that includes multi-pass shakedown effects. This paper presents a semi-analytical model to predict machining-induced RS in 3D turning operations, which are used representatively for 3D processes more generally. Rather than follow a ‘brute force’ 3D FEM approach or conduct countless experiments to train a purely data-driven machine learning algorithm, the proposed approach builds on previous 2D modeling work. Through careful consideration of the process physics, including complex geometry/kinematic considerations of 3D turning, the authors demonstrated an experimentally calibrated approach, as well as validation based on published RS data. Model predictions and previously published measurement data of RS depth profiles for turning of Inconel 718 were compared for a range of process parameters. Correlation between the proposed 3D model and validation data was found to be within the margin of experimental error for most conditions. The proposed model appears to capture the overall behavior of 3D RS depth profiles with acceptable accuracy, particularly the key metrics of near-surface stress, peak stress magnitude and location, as well as overall stress profile depth. This report presents a physics-informed, data-driven approach for efficient calibration of a 2D model for machining-induced RS through DIC analysis of in-situ characterized subsurface displacement fields.

42 ENGINEERING↗

Three-dimensional optical trapping and orientation of microparticles for coherent X-ray diffraction imaging

Optical trapping has been implemented in many areas of physics and biology as a noncontact sample manipulation technique to study the structure and dynamics of nano-andmesoscale objects. It provides a unique approach for manipulating microscopic objects without inducing undesired changes in structure. Combining optical trapping with hard X-ray microscopy techniques, such as coherent diffraction imaging and crystallography, provides a nonperturbing environment where electronic and structural dynamics of an individual particle in solution can be followed in situ. It was previously shown that optical trapping allows the manipulation of micrometer-sized objects for Xray fluorescence imaging. However, questions remain over the ability of optical trapping to position objects for X-ray diffraction measurements, which have stringent requirements for angular stability. Our work demonstrates that dynamic holographic optical tweezers are capable of manipulating single micrometer-scale anisotropic particles in a microfluidic environment with the precision and stability required for X-ray Bragg diffraction experiments-thus functioning as an "optical goniometer." The methodology can be extended to a variety of X-ray experiments and the Bragg coherent diffractive imaging of individual particles in solution, as demonstrated here, will be markedly enhanced with the advent of brighter, coherent X-ray sources.

Gao, Yuan↗

Measurement of the Deeply Virtual Neutral Pion Electroproduction Cross Section off the Proton at 10.6 GeV using the CLAS12 Detector

Deeply virtual exclusive reactions provide unique channels to study both transverse and longitudinal properties of the nucleon simultaneously, allowing for a 3D image of nucleon substructure. This presentation will discuss work towards extracting an absolute cross section for one such exclusive process, deeply virtual neutral pion production, using 10.6 GeV electron scattering data off a proton target from the CLAS12 experiment in Jefferson Lab Hall B. This measurement is important as exclusive meson production has unique access to the chiral odd Generalized Parton Distributions, and is also a background for other exclusive processes such as Deeply Virtual Compton Scattering, making the determination of this cross section crucial for other exclusive analyses.

Johnston, Robert↗

Event-Driven 3D Sensing Architecture

Some events happen too quickly to capture twice. Whether tracking satellites, monitoring aircraft, observing autonomous systems, or recording high speed industrial processes, imaging systems often have only one opportunity to collect the right information. If a camera is focused on the wrong distance, uses the wrong exposure, or cannot keep pace with rapid motion, important details may be lost forever. Los Alamos National Laboratory has developed an event-driven imaging architecture that preserves more information during data collection than a conventional camera. Instead of committing to a single image, the system captures data that can later be used to digitally adjust focus and exposure while reconstructing the scene in three dimensions. The result is a more flexible approach for imaging dynamic environments where conventional cameras can struggle.

42 ENGINEERING↗

System and method for adaptive range 3D scanning

A scanner system is configured for acquiring three dimensional image information of an object. The scanner includes a projector, a camera, a graphics processing device, and a processor. The projector projects one of several pre-defined patterns upon the object. The camera captures an image from the object, which is received by the processor. The processor approximates mutual information from the object and the pattern using the graphics processing device, and selects a second pattern for projecting on the object.

Rosman, Guy↗

WE-H-206-00: Advances in Preclinical Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

WE-H-206-02: Recent Advances in Multi-Modality Molecular Imaging of Small Animals

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗

WE-H-206-03: Promises and Challenges of Benchtop X-Ray Fluorescence CT (XFCT) for Quantitative in Vivo Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non-ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x-rays do. Consequently, high-resolution pure optical imaging (e.g., confocal microscopy, two-photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early-stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high-resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole-body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label-free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PAT Benjamin M. W. Tsui: Multi-modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi-modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi-pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high-resolution and artifact-free MPH and sparse-view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub-millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state-of-art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi-modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi-modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi-modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi-modality imaging instrumentation and techniques that are being developed. Sang Hyun Cho; X-ray fluorescence (XRF) imaging, such as x-ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal-based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imaging Funding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes: ;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH-12-1-0198.

60 APPLIED LIFE SCIENCES↗